Mycophenolate Mofetil

證據等級: L5

預測適應症: 10 個

Mycophenolate Mofetil: From Original Indication (Not Specified in Evidence Pack) to HIV Infectious Disease

One-Sentence Summary

Mycophenolate mofetil (MMF, DB00688) is an immunosuppressant whose original indication is not documented in this evidence pack. The TxGNN model predicts it may be effective for HIV Infectious Disease, with 10 clinical trials and 20 publications currently identified, though only a small subset directly test MMF as an HIV therapy and results are largely inconclusive.

Quick Overview

Item	Content
Original Indication	Not available in evidence pack (data gap)
Predicted New Indication	HIV Infectious Disease
TxGNN Prediction Score	99.86%
Evidence Level	L2
South Africa Market Status	Not Marketed
Number of SAHPRA Registrations	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

Detailed mechanism of action data for this drug is not available in the current evidence pack (data gap DG002). Based on the mechanistic rationale in the underlying prediction, MMF inhibits proliferation of activated T lymphocytes. Theoretically, this could reduce the pool of activated CD4+ T cells — the primary cellular target of HIV infection — and MMF has previously been explored as an adjunct to HAART to modulate the chronic immune hyperactivation seen in HIV disease.

However, this is an immunomodulatory mechanism rather than a direct antiviral one, and the original indication for this drug is not recorded here, so the relationship between the original indication and this new predicted indication cannot be assessed from the evidence pack alone.

Clinical evidence for MMF specifically in HIV is mixed: the MAN2 study (NCT00120419, Phase 4) directly tested MMF in untreated chronically HIV-1-infected patients but remains listed as UNKNOWN status with no confirmed outcome. Several smaller pharmacokinetic/cohort studies (e.g., PMID 12352149, 15213566) suggest MMF combined with certain antiretrovirals (notably abacavir) can transiently reduce plasma HIV-1 RNA via depletion of intracellular deoxyguanosine triphosphate, but sample sizes are small and findings have not been confirmed in a definitive controlled trial. Most of the higher-enrollment trials in the evidence set (transplant/GVHD studies) use MMF for its established immunosuppressive purpose in HIV-positive patients rather than as HIV therapy itself, and are only indirectly relevant.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00112593	N/A	Completed	5	Allogeneic HSCT in HIV-positive patients; MMF used as GVHD prophylaxis, not as HIV treatment
NCT00120419	Phase 4	Unknown	90	MAN2 Study: tests whether MMF reduces chronic immune hyperactivation and slows CD4+ T-cell decline in ART-naive HIV patients; no confirmed result on record
NCT00038272	Phase 2	Completed	56	DAPD vs. DAPD+MMF in treatment-experienced HIV patients; direct antiviral combination study
NCT02793544	Phase 2	Completed	80	HLA-mismatched unrelated donor BMT with post-transplant cyclophosphamide, sirolimus and MMF for GVHD prophylaxis in hematologic malignancies
NCT00021489	Phase 2	Withdrawn	0	MMF as adjunct to abacavir in treatment-failure HIV patients; withdrawn before enrollment, no data generated
NCT00247494	Phase 4	Unknown	90	MAN2 substudy evaluating MMF’s effect on cardiovascular surrogate markers in HIV-1 infection
NCT00009009	Phase 2	Completed	10	Renal transplantation in HIV-infected patients with end-stage renal disease; MMF used for rejection prophylaxis
NCT01453192	Phase 3	Completed	27	Clinical/immunological follow-up after renal transplantation in HIV-1-infected patients; immunosuppressive regimen includes MMF
NCT06869265	Phase 2	Recruiting	56	Thiotepa/busulfan/fludarabine conditioning for haplo-HSCT in elderly AML patients; MMF used for GVHD prophylaxis, not HIV-specific
NCT01288131	Phase 3	Terminated	8	Cyclosporine+MMF vs. cyclophosphamide+prednisolone for anti-EPO-associated PRCA; not related to HIV indication

No South African National Clinical Trials Register (SANCTR) or Pan African Clinical Trials Registry (PACTR) entries were identified in the evidence pack.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
15213566	2004	Randomized pilot study	J Acquir Immune Defic Syndr	MMF’s effect on immune response and plasma/lymphatic viral load during and after HAART interruption in chronic HIV infection
15353978	2004	Clinical study	AIDS	HAART with or without MMF in treatment-naive HIV-1 patients; effect on plasma RNA decay and latent reservoir
16379601	2005	Cohort	AIDS Res Hum Retroviruses	No detrimental immunological effects observed with MMF added to HAART in treatment-naive acute/chronic HIV-1 patients
15871638	2005	Cohort/PK	Clin Pharmacokinet	Pharmacokinetics/pharmacodynamics of low-dose MMF in HIV patients treated with abacavir, efavirenz and nelfinavir
15355127	2004	PK/PD study	Clin Pharmacokinet	Effect of MMF on pharmacokinetics of antiretrovirals and intracellular nucleoside triphosphate pools
12352149	2002	Cohort	J Acquir Immune Defic Syndr	Addition of MMF to abacavir-containing ART associated with dGTP depletion and decreased plasma HIV-1 RNA
11391161	2001	Pilot study	J Acquir Immune Defic Syndr	MMF as a component of multidrug-resistant HIV-1 salvage therapy in 7 heavily pre-treated AIDS patients
17885292	2007	Clinical study	AIDS	Amdoxovir (DAPD) with or without MMF in drug-resistant HIV infection
17017956	2006	Review	Curr Top Med Chem	Review of immunosuppressive drugs, including MMF, in HIV disease and immune activation
41118390	2025	Mechanistic/translational	J Clin Invest	Selective targeting of HIV-infected clonal CD4+ T cells by antiproliferative drugs (mechanistic rationale for antiproliferative approaches, including MMF-class agents)

South Africa Market Information

Mycophenolate mofetil currently has no SAHPRA registrations on record in this evidence pack; market status is Not Marketed (0 registered products).

Safety Considerations

Please refer to the SAHPRA-approved Professional Information (PI) for safety information. Report adverse drug reactions to SAHPRA.

Note: A Blocking data gap (DG001) was identified — TFDA/SAHPRA-equivalent product labelling (warnings and contraindications) is not currently available, which prevents completion of the initial safety screening (Stage S1) for this candidate.

Conclusion and Next Steps

Decision: Hold

Rationale: The prediction rests on a plausible but indirect immunomodulatory mechanism, and the most directly relevant trial (MAN2, NCT00120419) has no confirmed outcome (status: Unknown). Combined with a Blocking data gap on safety labelling and the drug’s absence from the South African market (0 SAHPRA registrations), the evidence is not yet sufficient to proceed even with guardrails.

To proceed, the following is needed:

SAHPRA-equivalent Professional Information (warnings, contraindications) to close the Blocking safety gap (DG001)
Confirmed mechanism of action data from DrugBank (DG002)
Outcome data from the MAN2 study (NCT00120419) and its cardiovascular substudy (NCT00247494)
Assessment of a South African market-entry pathway, since the product is not currently registered
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.